Imaging and Tissue Correlates to Optimize Management of Glioblastoma

描述（由申请人提供）：新P01的总体目标是将生理和代谢成像的进展与组织生物标志物相结合，以优化胶质母细胞瘤患者的管理。这将通过表征从初始表现到假定肿瘤进展的成像、遗传和表观遗传特征的变化来实现。所获得的信息将用于确定是否有可能为个体患者量身定制治疗策略，并将与以下药物联合使用： 超极化C-13代谢成像，以告知对治疗剂的早期反应。这些研究的结果将解决神经肿瘤学领域的关键挑战，并有可能对脑肿瘤患者的管理产生重大影响。 计划开展三个高度整合和协同的项目：项目1：通过整合成像和组织分析改善GBM管理。项目二：肿瘤异质性和演变的图像引导基因组-表观基因组分析和项目3：丙酮酸代谢的超极化碳13 MRSI监测以评估药物作用。P01的总体具体目标是： 1)准确定义治疗后环境中的肿瘤负荷。项目1和3将评估新型成像技术在评估肿瘤负荷方面的作用。 2)表征肿瘤内异质性（成像参数、组织学特征、遗传/表观遗传特征）以及对治疗反应、肿瘤演变和临床结局的影响。项目1和项目2将合并以实现这一目标。 3)评估对治疗的早期反应，以协助治疗决策。项目1和3将通过临床开发和应用超极化C-13成像结合生理和代谢成像技术来实现这一目标。 三个共享资源（行政和临床服务核心、生物标本和生物统计核心以及成像核心）将提供项目实现其目标所必需的关键服务。

DESCRIPTION (provided by applicant): The overall goal of the new P01 is to integrate advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with glioblastoma. This will be achieved by characterizing the evolution of changes in imaging, genetic and epigenetic profiles from the time of initial presentation until presumed tumor progression. The information obtained will be applied to determine whether it is possible to tailor treatment strategies to individual patients and will be used in combination with hyperpolarized C-13 metabolic imaging to inform on the early response to therapeutic agents. The results of these studies will address critical challenges in the field of Neuro-Oncology and have the potential to make a significant impact upon the management of patients with brain tumors. Three highly integrated and synergistic projects are planned: Project 1: Improved management of GBM by integrated imaging and tissue analysis. Project 2: Image guided genome-epigenome analysis of tumor heterogeneity and evolution and Project 3: Hyperpolarized carbon 13 MRSI monitoring of pyruvate metabolism to assess drug action. The overall specific aims of the P01 are: 1) To accurately define tumor burden in the post treated setting. Projects 1 and 3 will assess the role of novel imaging techniques to assess tumor burden. 2) To characterize intratumoral heterogeneity (imaging parameters, histologic characteristics, genetic/epigenetic features) and the effect on treatment response, tumor evolution and clinical outcome. Projects 1 and 2 will be integrated to accomplish this aim. 3) To assess early response to therapy to assist with treatment decisions. Projects 1 and 3 will accomplish this aim through the clinical development and application of hyperpolarized C-13 imaging in conjunction with physiological and metabolic imaging techniques. Three shared resources (Administrative and Clinical Services Core, Biospecimen and Biostatistics Core and the Imaging Core) will provide key services that are essential for the Projects to accomplish their aims.